Pancreatic arteriovenous malformation with pancreatitis involving a pancreatico-venous fistula

An arteriovenous malformation of the pancreas is a very rare disease, but its presentation is distinct and unique. In this report, we describe a patient who presented with this malformation which was localized in the tail of pancreas and demonstrated by abnormal angiography findings. The patient was a 60-year-old male with severe left hypochondralgia. Angiography revealed an increased blood volume in the tail of the pancreas with arteriovenous shunting. Secondary pancreatitis caused by the arteriovenous malformation was suspected by abnormal laboratory data, and confirmed by histology from the resected tail of the pancreas. This is a very rare report in which pancreatic arteriovenous malformation involving a pancreaticovenous fistula was confirmed by endoscopic retrograde cholangiopancreatography (ERCP).     

Identification and functional characterization of novel telomerase variant alleles in Japanese patients with bone-marrow failure syndromes

As the incidence of bone-marrow failure syndromes (BMFS) is 2-3x higher in East Asia than in the West, we examined peripheral blood or marrow cells of 100 Japanese patients for possible pathogenic mutations in the two main components of the telomere-synthesizing enzyme telomerase (hTERC RNA and hTERT protein) that have recently been implicated in the disease pathogenesis. We analyzed samples collected from 34 patients with acquired aplastic anemia (AA), 66 patients with myelodysplastic syndromes (MDS) and 120 healthy controls. In addition to two polymorphic germ-line sequence changes (n-771A/G and n-714 C insertion) in the promoter region of hTERC and eleven hTERT polymorphisms that were identified in both patients and healthy individuals, we found a novel germ-line C323T mutation in the hTERC RNA in an MDS patient only. This heterozygous C323T mutation abolished telomerase enzymatic activity and functioned in a haploinsufficiency manner to modulate telomerase activity in cells. In summary, this study reports a novel telomerase natural variant that abolishes telomerase function, which may lead to telomere shortening and marrow hypocellularity in patients with BMFS. This study also highlights the rarity of genetic alterations in BMFS patients in Japan, which suggests that other factors may play a more prominent role in the disease pathogenesis in East Asia.     

AAV8 vector expressing IL24 efficiently suppresses tumor growth mediated by specific mechanisms in MLL/AF4-positive ALL model mice

Mixed-lineage leukemia (MLL)/AF4-positive acute lymphoblastic leukemia (ALL) is a common type of leukemia in infants, which is associated with a high relapse rate and poor prognosis. IL24 selectively induces apoptosis in cancer cells and exerts immunomodulatory and antiangiogenic effects. We examined the effects of adeno-associated virus type 8 (AAV8) vector-mediated muscle-directed systemic gene therapy in MLL/AF4-positive ALL using IL24. In a series of in vitro studies, we examined the effects of AAV8-IL24-transduced C2C12 cell-conditioned medium. We also examined the effects of AAV8-IL24 in MLL/AF4 transgenic mice. The results revealed the effects of AAV8-IL24 in MLL/AF4-positive ALL both in vitro and in vivo. With regard to the mechanism of therapy using AAV8-IL24 in MLL/AF4-positive ALL, we demonstrated the antiangiogenicity and effects on the ER stress pathway and unreported pathways through inhibition of S100A6 and HOXA9, which is specific to MLL/AF4-positive ALL. Inhibition of S100A6 by IL24 was dependent on TNF-α and induced acetylation of p53 followed by activation of the caspase 8-caspase 3 apoptotic pathway. Inhibition of HOXA9 by IL24, which was independent of TNF-α, induced MEIS1 activation followed by activation of the caspase 8-caspase 3 apoptotic pathway. Thus, gene therapy using AAV8-IL24 is a promising treatment for MLL/AF4-positive ALL.     

Age-related change of neurochemical abnormality in attention-deficit hyperactivity disorder: A meta-analysis

Prevalence and symptoms of attention-deficit hyperactivity disorder (ADHD) change with advancing age. However, neurochemical background of such age-related change is yet to be elucidated. We therefore conducted a meta-analysis of 16 proton magnetic resonance spectroscopy studies comprising 270 individuals with ADHD and 235 controls. Standardized mean differences were calculated and used as an effect size. Sensitivity analyses and meta-regression to explore the effect of age on neurochemical abnormality were performed. A random effects model identified a significantly higher-than-normal N-acetylaspartate (NAA) in the medial prefrontal cortex (mPFC), but no significant differences of other metabolites in that area. No significant difference in metabolite levels was demonstrated in any other region. Sensitivity analysis of children with ADHD revealed significantly higher-than-normal NAA, whereas no significant difference was found in adults with ADHD. Meta-regression revealed significant correlation between advanced age and normal levels of NAA in the mPFC, suggesting that age-dependent abnormality of NAA level in the mPFC is a potential neural basis of age-related change of symptoms of ADHD.     

Prevalence and trends of underweight and BMI distribution changes in Japanese teenagers based on the 2001 National Survey data

BACKGROUND: Excessive thinness has been glamorized among Japanese adolescent girls, and unhealthy dieting to lose weight has become a popular practice among them. The prevalence of underweight in contemporary Japanese girls in comparison with that of boys, however, remains to be studied. AIM: The purpose of this study was to determine the prevalence and trends of underweight in contemporary Japanese teenagers of both sexes using nationally representative cross-sectional data. SUBJECTS AND METHODS: Underweight was defined as BMI < 3rd percentile by age and sex of the 1978-1981 reference population as previously reported. These reference values were compared with BMIs of the contemporary population based on the 2001 Cross-sectional National Survey data of Japanese teenagers (215 972 boys and 216 496 girls). RESULTS: The prevalence of underweight was approximately 2-3% in junior high school students of both sexes, 12.5-14.5 years of age, approximately 3% in senior high school students of both sexes, 15.5-16.5 years of age, and approximately 4% in senior high school students of both sexes, 17.5 years of age. CONCLUSION: The prevalence of underweight decreased among Japanese teenage students of both sexes during the past decades. Female preponderance in the prevalence of underweight was not confirmed.     

Motor discoordination of transgenic mice overexpressing a microtubule destabilizer, stathmin, specifically in Purkinje cells

The proper regulation of microtubule (MT) structure is important for dendritic and neural circuit development. However, the relationship between the regulation of the MTs in dendrites and the formation of neural function is still unclear. Stathmin is a MT destabilizer, and we have previously reported that the expression and the activity of stathmin is downregulated during cerebellar Purkinje cell (PC) development. In this study, we generated transgenic mice that specifically overexpress the constitutively active form of stathmin in the PCs. These mutant mice did not show any obvious morphological or excitatory transmission abnormalities in the cerebellum. In contrast, we observed a decline in the expression of MAP2 and KIF5 signal in the PC dendrites and a discoordination of motor function in the mutant mice, although they displayed normal general behavior. These data indicate that the overexpression of stathmin disrupts dendritic MT organization, motor protein distribution, and neural function in PCs.     

Acute oral selenium intoxication with ten times the lethal dose resulting in deep gastric ulcer

A 48-year-old woman presented after taking 2000 mg of selenium dioxide, corresponding to 10 times the experimental lethal dose in animals. She presented with mildly altered consciousness and hematemesis. Endoscopy revealed mucosal damage throughout the oral cavity, esophagus, and stomach. There was no evidence of perforation. After intubation and gastric lavage, hemodialysis was performed. The patient was discharged uneventfully on the 16(th) day. This case highlights a very rare acute selenium intoxication. Serum and urinary selenium levels and serum glutathione peroxidase activities during the patient's course were followed, as well as the mucosal corrosive damage caused by the selenium.